The objective of the Retrovirus Epidemiology Donor Study-II (REDS-II) is to conduct epidemiological, laboratory, and survey research on volunteer blood donors to ensure the safety and availability of the blood supply. This includes monitoring known blood-borne infectious agents, rapidly evaluating the impact of emerging pathogens, assessing the safety implications of changes in laboratory and/or blood donor screening protocols, and examining blood supply and availability issues. Addressing issues concerned with the safety and availability of the blood supply serves as the cornerstone of REDS-II. The study consists of a coordinating center, six blood centers, and a central laboratory.